👤 James N Cobley

Proteomics has matured into a discipline capable of quantifying nearly every protein encoded by the genome, yet it remains largely blind to the true operational units of physiology: proteoforms. Each proteoform—defined by a specific sequence and post-translationally modified state—represents a unique molecular identity with distinct chemical, functional, and structural properties. This review proposes the proteoform functor: a mathematical map between the abstract proteoform state space and the realised physiological space of biological function—and ultimately complex phenotypes. This mapping is not linear or additive. Rather, it is hierarchical, nonlinear, and context-dependent, reflecting the emergent complexity of life. Without resolving proteoforms, proteomics risks describing shadows of biology rather than its material substance. Deciphering complex phenotypes, demands a shift from bulk protein averages to revealing the precise molecular identities—proteoforms—that give rise to physiology. Show less